Variant chr10-113725526-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP3BP4_StrongBP6_ModerateBS2

The NM_001227.5(CASP7):c.541T>C(p.Phe181Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00335 in 1,551,130 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 19 hom. )

Consequence

CASP7
NM_001227.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.03

Variant links:

Genes affected

CASP7 (HGNC:1508): (caspase 7) This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. The precursor of the encoded protein is cleaved by caspase 3 and 10, is activated upon cell death stimuli and induces apoptosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

CASP7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 8: AlphaMissense, BayesDel_noAF, Cadd, Eigen, FATHMM_MKL, MutationAssessor, PROVEAN, REVEL [when BayesDel_addAF, max_spliceai, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.0149098635).

BP6

Variant 10-113725526-T-C is Benign according to our data. Variant chr10-113725526-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2640854.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 531 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASP7	NM_001227.5 linkuse as main transcript	c.541T>C	p.Phe181Leu	missense_variant	5/7	ENST00000369318.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASP7	ENST00000369318.8 linkuse as main transcript	c.541T>C	p.Phe181Leu	missense_variant	5/7	1	NM_001227.5	P1	P55210-1

Frequencies

GnomAD3 genomes

AF:

0.00350

AC:

532

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.0223

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00360

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00427

AC:

859

AN:

201296

Hom.:

AF XY:

0.00436

AC XY:

477

AN XY:

109326

show subpopulations

Gnomad AFR exome

AF:

0.000545

Gnomad AMR exome

AF:

0.000535

Gnomad ASJ exome

AF:

0.00384

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00282

Gnomad FIN exome

AF:

0.0203

Gnomad NFE exome

AF:

0.00351

Gnomad OTH exome

AF:

0.00397

GnomAD4 exome

AF:

0.00333

AC:

4664

AN:

1398822

Hom.:

Cov.:

AF XY:

0.00333

AC XY:

2304

AN XY:

691250

show subpopulations

Gnomad4 AFR exome

AF:

0.000297

Gnomad4 AMR exome

AF:

0.000597

Gnomad4 ASJ exome

AF:

0.00230

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00237

Gnomad4 FIN exome

AF:

0.0170

Gnomad4 NFE exome

AF:

0.00309

Gnomad4 OTH exome

AF:

0.00293

GnomAD4 genome

AF:

0.00349

AC:

531

AN:

152308

Hom.:

Cov.:

AF XY:

0.00420

AC XY:

313

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000601

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.0223

Gnomad4 NFE

AF:

0.00359

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00281

Hom.:

Bravo

AF:

0.00169

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00337

AC:

ExAC

AF:

0.00348

AC:

423

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

CASP7: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Benign

-0.019

BayesDel_noAF

Pathogenic

0.20

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

T;T;T;T;T;T;.;.

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

D;D;.;D;.;.;D;D

MetaRNN

Benign

0.015

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.33

MutationAssessor

Pathogenic

3.1

M;.;M;.;M;M;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.70

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D;D

Polyphen

1.0

D;.;D;.;D;D;D;.

Vest4

0.85

MutPred

0.73

Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);.;Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);.;.;

MVP

0.85

MPC

0.72

ClinPred

0.049

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.98

gMVP

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over